'À La Carte' Cyclic Hexapeptides: Fine Tuning Conformational Diversity while Preserving the Peptide Scaffold. Issue 8 (27th February 2018)

• Record Type: Journal Article
• Authors: Ciudad, Sonia; Bayó‐Puxán, Núria; Varese, Monica; Seco, Jesús; Teixidó, Meritxell; García, Jesús; Giralt, Ernest
• Is Part Of: ChemistrySelect. Volume 3:Issue 8(2018)
• Page Start: 2343
• Page End: 2351
• Publication Date: 2018-02-27
• Subjects: Amino acids -- conformation analysis -- NMR spectroscopy -- peptides -- structure elucidation; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201800254
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Cyclic peptides have recently emerged as promising modulators of challenging protein‐protein interactions. Here we report on the design, synthesis and conformational behavior of a small library composed of C2 symmetric cyclic hexapeptides of type c(Xaa‐D‐Pro‐Yaa)2, where Xaa and Yaa are chosen from alanine, isoleucine, serine, glutamic acid, arginine and tryptophan due to the favorable properties of the side chains of these residues to recognize complex protein surfaces. We used a combination of nuclear magnetic resonance and molecular dynamic simulations to perform an extensive conformational analysis of a representative set of cyclic hexapeptides. Our results indicated that both the chemical nature and the chirality of the variable Xaa and Yaa positions play an important role in the cis/trans configuration of the Xaa‐D‐Pro bonds and in the conformational preferences of this family of peptides. This structural tuning can be exploited in design strategies seeking to optimize the binding efficiency and selectivity of cyclic hexapeptides towards protein surfaces. Abstract : Structural tuning of cyclic hexapeptides: we have found that conformational diversity in symmetric cyclic hexapeptides can be modulated by changing the chemical nature and stereochemistry of their residues. Using NMR and MD, we have extensively analysed the conformational preferences of a family of cyclic hexapeptides.